In which scenarios should patients with Type 2 Diabetes (T2D) initiate Glucagon-Like Peptide-1 (GLP-1) or Sodium-Glucose Cotransporter 2 (SGLT2) therapy as first-line treatment instead of Metformin?

From the Guidelines

Patients with Type 2 Diabetes should start with a GLP1 or SGLT2 therapy as first-line instead of metformin in scenarios where they have established atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD) with an eGFR ≥20 ml/min/1.73 m², or a compelling need for weight loss, as these therapies have demonstrated significant cardiovascular and renal protective effects beyond glucose control, as supported by the most recent guidelines 1. The decision to initiate GLP1 or SGLT2 therapy as first-line treatment is based on the patient's specific clinical profile and the presence of certain comorbidities.

• For patients with ASCVD, GLP-1 agonists such as semaglutide, dulaglutide, or liraglutide are preferred due to their established benefits in reducing major adverse cardiovascular events, as noted in recent studies 1.
• For those with heart failure or CKD, SGLT2 inhibitors like empagliflozin, dapagliflozin, or canagliflozin are recommended because they have been shown to slow the progression of CKD and reduce the risk of cardiovascular outcomes, including data from dedicated kidney outcomes trials 1.
• Patients with obesity may benefit from GLP-1 agonists due to their significant weight loss effects, which can contribute to improved glycemic control and reduced cardiovascular risk, as highlighted in the latest standards of care in diabetes 1. It's essential to consider the potential side effects of these medications, such as gastrointestinal symptoms with GLP-1 agonists or genital infections and volume depletion with SGLT2 inhibitors, and to monitor patients closely to adjust therapy as needed, taking into account the most current clinical evidence and guidelines 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Scenarios for Initiating GLP1 or SGLT2 Therapy as First-Line

The following scenarios are identified where patients with Type 2 Diabetes may start with a GLP1 or SGLT2 therapy as first-line instead of metformin:

• Patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, where GLP1 receptor agonists or SGLT2 inhibitors are recommended as first-line therapy due to their cardiovascular benefits 2, 3
• Patients at high risk of cardiovascular disease, where GLP1 receptor agonists may be considered as first-line therapy 3
• Patients with heart failure (with reduced ejection fraction) or chronic kidney disease (with or without established cardiovascular disease), where SGLT2 inhibitors may be considered as first-line therapy 3
• Patients with contraindications to metformin, such as renal impairment or gastrointestinal intolerance, where GLP1 receptor agonists or SGLT2 inhibitors may be considered as alternative first-line therapies

Key Considerations

When considering GLP1 or SGLT2 therapy as first-line, the following factors should be taken into account:

• The patient's individual risk factors and comorbidities, such as cardiovascular disease, heart failure, or chronic kidney disease
• The potential benefits and risks of GLP1 receptor agonists and SGLT2 inhibitors, including their effects on glycemic control, weight, blood pressure, and cardiovascular outcomes
• The cost-effectiveness of these therapies, which may vary depending on the patient's specific circumstances and the healthcare system in which they are being treated 4
• The availability of alternative therapies and the patient's preferences and values 5